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结肠癌细胞系中依赖细胞外基质的信号通路揭示了抗癌治疗的潜在靶点。

Extracellular Matrix-dependent Pathways in Colorectal Cancer Cell Lines Reveal Potential Targets for Anticancer Therapies.

作者信息

Stankevicius Vaidotas, Vasauskas Gintautas, Noreikiene Rimante, Kuodyte Karolina, Valius Mindaugas, Suziedelis Kestutis

机构信息

Laboratory of Molecular Oncology, National Cancer Institute, Vilnius, Lithuania Department of Biochemistry and Molecular Biology, Faculty of Natural Sciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania.

Proteomics Center, Vilnius University Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania.

出版信息

Anticancer Res. 2016 Sep;36(9):4559-67. doi: 10.21873/anticanres.11004.

DOI:10.21873/anticanres.11004
PMID:27630296
Abstract

BACKGROUND

Cancer cells grown in a 3D culture are more resistant to anticancer therapy treatment compared to those in a monolayer 2D culture. Emerging evidence has suggested that the key reasons for increased cell survival could be gene expression changes in cell-extracellular matrix (ECM) interaction-dependent manner.

MATERIALS AND METHODS

Global gene-expression changes were obtained in human colorectal carcinoma HT29 and DLD1 cell lines between 2D and laminin-rich (lr) ECM 3D growth conditions by gene-expression microarray analysis. The most significantly altered functional categories were revealed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.

RESULTS

The microarray data revealed that 841 and 1190 genes were differentially expressed in colorectal carcinoma DLD1 and HT29 cells. KEGG analysis indicated that the most significantly altered categories were cell adhesion, mitogen-activated protein kinase and immune response.

CONCLUSION

Our results indicate altered pathways related to cancer development and progression and suggest potential ECM-regulated targets for the development of anticancer therapies.

摘要

背景

与单层二维培养的癌细胞相比,在三维培养中生长的癌细胞对抗癌治疗更具抗性。新出现的证据表明,细胞存活增加的关键原因可能是以细胞 - 细胞外基质(ECM)相互作用依赖的方式发生的基因表达变化。

材料与方法

通过基因表达微阵列分析,在二维和富含层粘连蛋白(lr)的ECM三维生长条件下,获得了人结肠直肠癌HT29和DLD1细胞系中的全局基因表达变化。通过京都基因与基因组百科全书(KEGG)通路富集分析揭示了最显著改变的功能类别。

结果

微阵列数据显示,在结肠直肠癌DLD1和HT29细胞中分别有841个和1190个基因差异表达。KEGG分析表明,最显著改变的类别是细胞粘附、丝裂原活化蛋白激酶和免疫反应。

结论

我们的结果表明与癌症发展和进展相关的通路发生了改变,并提示了潜在的ECM调节靶点,用于开发抗癌疗法。

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